Interrogating cell type-specific cooperation of transcriptional regulators in 3D chromatin
Xianfu Yi,
Zhanye Zheng,
Hang Xu,
Yao Zhou,
Dandan Huang,
Jianhua Wang,
Xiangling Feng,
Ke Zhao,
Xutong Fan,
Shijie Zhang,
Xiaobao Dong,
Zhao Wang,
Yujun Shen,
Hui Cheng,
Lei Shi,
Mulin Jun Li
Affiliations
Xianfu Yi
School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin 300070, China; Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Corresponding author
Zhanye Zheng
Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Hang Xu
Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China
Yao Zhou
Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Dandan Huang
Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Jianhua Wang
Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Xiangling Feng
Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Ke Zhao
Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Xutong Fan
Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Shijie Zhang
Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Xiaobao Dong
Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Zhao Wang
Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Yujun Shen
Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Hui Cheng
State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences, Tianjin 300070, China
Lei Shi
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Mulin Jun Li
Department of Bioinformatics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Department of Epidemiology and Biostatistics, Tianjin Key Laboratory of Molecular Cancer Epidemiology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300070, China; Corresponding author
Summary: Context-specific activities of transcription regulators (TRs) in the nucleus modulate spatiotemporal gene expression precisely. Using the largest ChIP-seq data and chromatin loops in the human K562 cell line, we initially interrogated TR cooperation in 3D chromatin via a graphical model and revealed many known and novel TRs manipulating context-specific pathways. To explore TR cooperation across broad tissue/cell types, we systematically leveraged large-scale open chromatin profiles, computational footprinting, and high-resolution chromatin interactions to investigate tissue/cell type-specific TR cooperation. We first delineated a landscape of TR cooperation across 40 human tissue/cell types. Network modularity analyses uncovered the commonality and specificity of TR cooperation in different conditions. We also demonstrated that TR cooperation information can better interpret the disease-causal variants identified by genome-wide association studies and recapitulate cell states during neural development. Our study characterizes shared and unique patterns of TR cooperation associated with the cell type specificity of gene regulation in 3D chromatin.
